This proposal is a competing renewal of our current research project. Neuropathological changes related to Alzheimer's Disease (AD) may begin 20 to 30 years before the onset of clinical symptoms in individuals at great risk. AD affects an estimated 4.5 million Americans and is expected to affect as many as 16 million Americans by 2050, as the baby boomers reach the age at which they are most at risk. It is of major concern to explore and develop new technologies for the early detection of AD in order to facilitate disease prevention, diagnosis, and effective treatment. The goal of this RO1 proposal is to develop an innovative imaging technology for the early detection of AD. We propose a new composite MRI Neuroimaging (MRN) Index, obtained by quantitatively combining two fMRI measurements: Functional Connectivity Index (FCI) and Regional Cerebral Blood Flow (rCBF)-Perfusion Deficits at the resting-state condition. To validate this Index as a marker, we first test whether it can cross-sectionally distinguish mild AD from cognitive normal (CN) subjects and distinguish mild AD from other types of non-AD dementia, such as frontotemporal dementia (FTD) and vascular dementia (VaD). Second, we test whether the MRN Index can retroactively predict mild cognitive impairment (MCI) subjects who converted to AD from those who did not. Third, we will determine the dynamic characteristics of the MRN Index in predicting the onset of AD dementia in MCI subjects during the longitudinal studies.